Jump to

Abstract

Introduction: Poor cell viability of mesenchymal stem cells (MSCs) after transplantation has limited their reparative capability. Previous studies reported that vagal stimulation (VS) has anti-apoptotic effects and anti-inflammatory effects in various pathological conditions. We hypothesized that VS enhances the protective effects of MSCs in repair of ischemic myocardium.

Methods: At 1 h after left coronary artery ligation, MSCs (5 × 106 cells) expressing green fluorescent protein (GFP) were injected into the ischemic rat myocardium, followed by VS (VS-MSC) or sham stimulation (SS-MSC) for 4 weeks. In control group, PBS was injected and sham stimulation was performed. We implanted a radio-controlled stimulator for VS. The stimulation intensity was adjusted for each rat to lower heart rate by 20–30 beats/min. At the end of 4-week treatment, the impact of VS was evaluated by means of echocardiography, cardiac catheterization, neurohumoral states, immunohistochemistry and histological examination. Homing of MSCs to the heart was assessed by the number of GFP positive cells in the 8 tissue sections (2 mm interval) per animal.

Results: VS-MSC therapy significantly prevented the progression of ventricular remodeling and improved indices of cardiac function (table⇓). The number of viable transplanted cells was higher in VS-MSC group than in SS-MSC group (3467±702 vs. 2452±907 cells, p<0.05). Microvessel density as shown by v-WF positive cells was higher in VS-MSC group than in SS-MSC group (1678±398 vs. 1141±317 vessels/mm2, p< 0.01). Double staining of the sections for cardiac-specific proteins showed that GFP positive cells expressed myosin heavy chain, cardiac troponin I, desmin and connexin-43. GFP were negative for α-smooth muscle actin-positive cells.

Conclusion: Chronic VS enhanced the therapeutic potency of MSCs. These beneficial effects may be mediated partly by enhancement of survival of transplanted MSCs and induction of angiogenesis.

Effects of VS and MSCs transplantation on ventricular remodeling and function after MI